This research proposal contains three separate research projects, I-III. Project I aims at the elucidation of the tertiary structure of a functionally important NH2-terminal domain (N-DSK) of the fibrinogen molecule. We propose to crystallize this structure and subsequently by means of X-ray crystallography deduce its three-dimensional structure. In Project II we propose to study structures in fibrinogen which have potential immunosuppressive action. In this project the active peptides will be obtained from fibrinogen digested with plasmin or trypsin. Also fragments obtained by cleavage with CNBr will be studied in regard of immunosuppressive action. We intend to identify the active peptides in the structure of fibrinogen. In project III we propose to isolate and characterize the components of the factor VIII complex. This project consists of two parts. In the first phase we intend to produce a clinically useful factor VIII preparation of high specific activity containing F VIII:C and the factor missing in v. Willebrand disease. In the next phase we propose to further purify the factor VIII complex and its constituent components F VIII:C/F VIII:CAG, F VIII:RAG/F VIII:RCF. In this last part of the project thioredoxin will be used to dissociate the components of the complex which will be separated by gel filtration and isotachophoretic procedures.